创作:花开 审核:aluba 2018年03月06日
  • 在原发性正常和肝癌组织中,临床级别的溶瘤正呼肠孤病毒(Reo)刺激先天性免疫,无细胞毒性作用,且不依赖于病毒基因组复制,需要IFN介导的NK细胞的活化;
  • 通过激活先天性脱粒免疫细胞,Reo诱导细胞因子应答以抑制HCV复制,对肝细胞癌(HCC)临床前模型有效;
  • Reo诱导的先天性免疫应答对HBV相关HCC及EBV相关淋巴瘤亦有效,Reo优于溶瘤病毒(OV);
  • Reo及其他选择性促炎症OV可用于治疗致癌病毒感染相关的多种肿瘤。
Gut [IF:23.059]

Oncolytic reovirus as a combined antiviral and anti-tumour agent for the treatment of liver cancer



2016-11-15, Article

Abstract & Authors:展开

OBJECTIVE: Oncolytic viruses (OVs) represent promising, proinflammatory cancer treatments. Here, we explored whether OV-induced innate immune responses could simultaneously inhibit HCV while suppressing hepatocellular carcinoma (HCC). Furthermore, we extended this exemplar to other models of virus-associated cancer.
DESIGN AND RESULTS: Clinical grade oncolytic orthoreovirus (Reo) elicited innate immune activation within primary human liver tissue in the absence of cytotoxicity and independently of viral genome replication. As well as achieving therapy in preclinical models of HCC through the activation of innate degranulating immune cells, Reo-induced cytokine responses efficiently suppressed HCV replication both in vitro and in vivo. Furthermore, Reo-induced innate responses were also effective against models of HBV-associated HCC, as well as an alternative endogenous model of Epstein-Barr virus-associated lymphoma. Interestingly, Reo appeared superior to the majority of OVs in its ability to elicit innate inflammatory responses from primary liver tissue.
CONCLUSIONS: We propose that Reo and other select proinflammatory OV may be used in the treatment of multiple cancers associated with oncogenic virus infections, simultaneously reducing both virus-associated oncogenic drive and tumour burden. In the case of HCV-associated HCC (HCV-HCC), Reo should be considered as an alternative agent to supplement and support current HCV-HCC therapies, particularly in those countries where access to new HCV antiviral treatments may be limited.

First Authors:
Alan Melcher,Stephen Griffin

Correspondence Authors:
Stephen Griffin

All Authors:
Adel Samson,Matthew J Bentham,Karen Scott,Gerard Nuovo,Abigail Bloy,Elizabeth Appleton,Robert A Adair,Rajiv Dave,Adam Peckham-Cooper,Giles Toogood,Seishi Nagamori,Matthew Coffey,Richard Vile,Kevin Harrington,Peter Selby,Fiona Errington-Mais,Alan Melcher,Stephen Griffin